The long term objective of this research is to determine the importance of natural killer (NK) cell activity in host defense against oral ulcerative diseases caused by herpes simplex virus (HSV). Recurrent herpes labialis is one of the most common viral afflictions of man. Since persons with recurrent lesions have high concentrations of neutralizing antibody and immune lymphocytes, something other than these specific effector functions must be important in the control of recurrent viral lesions. The specific question posed in this work is, do persons with herpes labialis differ from those with no recent history of oral lesions, in the in vitro response of their NK cells to HSV-1. Individual differences in spontaneous and HSV-1 boosted NK activity will be correlated with occurrence and recurrence of herpes labialis. Subjects with oral lesions typical of herpes labialis will be recruited from patients seen in the Howard University Dental Clinic. Age and sex matched controls (i.e., no recall of recent fever blisters), will be recruited from the normal adult population. Blood samples will be obtained from the affected group at the time of a lesion and 2-6 weeks later, when the lesion has disappeared. Controls will be tested at comparable time periods. Since NK activity has been associated morphologically with large granular lymphocytes (LGL), LGL enriched preparations will be isolated from peripheral blood leukocytes by a series of stepwise separations techniques, including Ficoll-Hypaque density gradient centrifugation, selective depletion of monocytes by plastic adherence and B-lymphocytes by nylon wool adherence, Percoll density gradient centrifugation, antibody plus complement depletion of T-lymphocytes and fluorexent antibody cell sorting. HSV-1 infection of LGL will be evaluated in the infectious center assay using vero cell monolayers. The interaction of HSV-1 and LGL will also be evaluated on the basis of interferon (IFN) production, which will be assayed by plaque inhibiton of vesicular stomatitis virus on monolayers of human foreskin fibroblasts. LGL from affected and control groups will be tested for spontaneous, HSV-1 boosted and IFN boosted NK activity. Since LGL are naturally occurring cells that: 1) spontaneously lyse HSV-1 infected cells: 2) can be boosted in cytotoxic activity by IFN; and 3) release IFN upon stimulation with HSV, the results of this study should be useful in the further characterization of immunological aspects of herpes infection and in assessing LGL as effectors and/or regulatory cells in the immune response to oral ulcerative diseases.